Species

mitogen activated protein kinase 3

Summary

Summary: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.

..Erk activity is essential for the process of positive selection, and it differentially affects CD4 and CD8 T cell maturation; yet, diminished expression itself is not sufficient to alter lineage commitment...

..The inhibition of ERK1/2 activation in vitro and in vivo by compounds targeting the EGF receptor points to the interest of ERK1/2 as potential surrogate markers of EGF-receptor signaling in clinical therapeutic studies...

Raf-1 kinase is required for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload

..Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK(ERK1,2) activation...

ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF

..Our results reveal an unexpected complexity of ERK-dependent signaling in the brain and a critical regulatory role for ERK1 in the long-term adaptive changes underlying striatum-dependent behavioral plasticity and drug addiction...

..Thus, membrane-associated forms of estrogen receptor may play a role in promoting intracellular signaling for hormone-mediated proliferation and survival of breast cancers and offer a new target for antitumor therapy...

Mechanisms regulating the constitutive activation of the extracellular signal-regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of ribonucleic acid interference for ERK1/2 on cancer cell proliferation

..These results provide evidence that the ERK pathway plays a major role in ovarian cancer pathogenesis and that down-regulation of this master signaling pathway is highly effective for the inhibition of ovarian tumor growth...

Tae Wook ChungNational Research Laboratories for Glycobiology, Ministry of Science and Technolgoy, and Department of Biochemistry and Molecular Biology, College of Oriental Medicine, Dongguk University, Kyungju, South KoreaFASEB J 18:1123-5. 2004

..These results clearly suggest that the HBx contributed to the transcriptional regulation of MMP-9 through the ERKs and PI-3K-AKT/PKB pathway, and increased an invasive potential of cells...

A mitochondrial kinase complex is essential to mediate an ERK1/2-dependent phosphorylation of a key regulatory protein in steroid biosynthesis

..Erk1/2 phosphorylation was slightly reduced but still evident in JIMT-1 cells. We conclude that the JIMT-1 cell line provides a valuable experimental model for studies of new trastuzumab-resistance mechanisms...

..Hence, the nucleus is a critical site for mitogenic signal termination by: (1) nuclear sequestration of p42/p44 MAPKs away from MEK, their cytoplasmic activator; and (2) dephosphorylation by specific nuclear phosphatases...

High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome

..These results demonstrate that RA, by a nongenomic mechanism, stimulates signaling pathways that lead to phosphorylation of transcription factors, which in turn activate the transcription of genes involved in neuronal differentiation...

..Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1...

..Therefore, the present data support a possible role for human adult pancreatic duct cells, following expansion and transdifferentiation, as a source of insulin by transplantation to type I diabetes patients...

Adhesion-dependent activation of the ERK1/2 cascade is by-passed in melanoma cells

..Collectively, these results indicate that calcineurin-NFAT and MEK1-ERK1/2 pathways constitute a codependent signaling module in cardiomyocytes that coordinately regulates the growth response through two distinct mechanisms...

Extracellular signal-regulated kinases are involved in the acute activation of steroidogenesis in immature rat Leydig cells by human chorionic gonadotropin

..Taken together, our results demonstrate new aspects of the glucose-dependent actions of ERK1/2 in beta-cells exerted on cytoplasmic proteins, including synapsin I, and participating in the overall glucose-induced insulin secretion...

The RasGAP-binding protein p62dok is a mediator of inhibitory FcgammaRIIB signals in B cells

I TamirDepartment of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver 80206, USAImmunity 12:347-58. 2000

..Using chimeric FcgammaRIIB containing the RasGAP-binding domain of p62dok, we demonstrate that p62dok contains all structural information required to mediate the inhibitory effect of FcgammaRIIB on Erk activation...

..Taken together, these findings suggest that ERK phosphorylation in spinal cord neurones plays an important role in chronic inflammatory articular pain and that its inhibition may provide significant anti-nociception...

..This evaluation of downstream signaling revealed that E(2)-induced Erk activation is mediated by a HRG/HER-2/PKC-delta/Ras pathway that could be crucial for E(2)-dependent growth-promoting effects in early stages of tumor progression...

Using U0126 to dissect the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in the regulation of gene expression by endothelin-1 in cardiac myocytes

..These results demonstrate that TAM-R MCF-7 cell growth is mediated by the autocrine release and action of an EGFR-specific ligand inducing preferential EGFR/c-erbB2 dimerization and downstream activation of the ERK pathway...

..Co-expression of both constitutively activated p38 and ERK1/2, however, could partially mimic the pro-motility effects of collagen and GF. This study reveals for the first time the specific functions of ECM and GF in cell motility...

Effects of pertussis toxin on extracellular signal-regulated kinase activation in hepatocytes by hormones and receptor-independent agents: evidence suggesting a stimulatory role of G(i) proteins at a level distal to receptor coupling

..Our findings support a broader role of FRS2 in EGFR-controlled signaling pathways in A-431 cells and provide insight into a molecular mechanism for ligand-stimulated feedback regulation with FRS2 as a central regulatory switch point...

..An additional Specific Aim IV will use the HPME cell line to confirm the key observations made from OFPAE cells. These studies will glean important information on the mechanisms regulating placental angiogenesis. ..

..This information could be applied to not only stimulate neural regeneration to treat sight-threatening diseases of the retina, but also to control gliosis that may be detrimental to the pathogenesis of retinal disorders. ..

..Through an enhanced understanding of these mechanisms it is our goal that potential therapeutic targets may be discovered to regulate the inflammatory response following trauma/hemorrhage and ischemia/reperfusion. ..

..Determine the side effects and complications of SOCE inhibition after shock. 3. Determine the effects of injury on intracellular S1P/SOCE signaling 4. Determine the mechanisms by which circulating S1P activates PMN after trauma. ..

..Exploring these mechanisms will expand the scientific rationale for tyrosine kinase inhibition as a therapeutic approach to asthmatic airway remodeling, and justify further study of the therapeutic role of soy isoflavones. ..

..The long-range goal of this work is to broaden our understanding of medulloblastoma growth, so that novel biologic therapies may be developed into new treatments for medulloblastoma, the most common malignant brain tumor in children. ..

..Little is known how these molecules function in the embryonic lung and what genes they regulate. This study will provide insights into this issue and will help to understand mechanism of human diseases. ..

..The results of these studies are expected to have an impact on our understanding of the biology of Tpo in heart and may lead to the development of new therapeutics for the treatment of myocardial infarction. ..

..From these results a neuronal "E2-signature cDNA array" will be developed and used in Aim 3 to determine how environmental estrogens influence E2-responsive gene expression in these developing neurons. ..

..Our hope is that by the end of the grant period, we will be able to provide a pyrrhocoricin-derived peptide for ensuing US Food and Drug Administration-approved preclinical and clinical evaluation against urinary tract infections. ..

..The results of this study are essential to understand the molecular basis of deranged metabolism in sepsis. Understanding the mechanism might be useful for developing appropriate therapeutic intervention during sepsis. ..

..Dissection of the role of cell cycle and survival regulators in proliferative and apoptotic responses to the combined effects of asbestos and N02 may lead to new biomarkers for exposure of the human lung to chemical mixtures. ..

..Aim four is to characterize the activation, enzymatic properties, and functions of MAPKAP kinase-like enzymes (Rcklp, Rck2p) in yeast, a model eukaryote, using combined biochemical and genetic approaches. ..

..If we are successful in purifying the novel GP-R (and confirm its role in mediating the mitogenic effects of gastrins) then one can develop systemic strategies to block the receptor mediated effects in future funding periods. ..

..3. To provide partial support to students and junior faculty to attend the meeting. They request funds for the 2003 meeting as well as for the 2 subsequent PASPCR annual meetings in years 2004 and 2006. ..

..Results from the proposed research are expected to yield new insights into the molecular mechanisms that control neurotransmitter receptor density at the NMJ, which may bear on such control at synapses in the brain. ..

..Altogether, the results are likely to generate a novel marker(s) that can be used to assess propensity for malignant transformation, tumor progression and/or sensitivity to chemotherapeutic drugs that target chromatin conformation. ..

..The insights provided by these investigations are likely to develop rational use of IL-21 alone or in combination with other cytokines for the therapy of cancer, infectious diseases, autoimmunity and transplantation. ..

..These studies will provide information concerning the mechanism of CNS cellular gene activation by Tat, and may serve as an initial step toward the development of targeted therapeutic compounds against HIV-1 Tat in the CNS. ..